Second generation HIV protease inhibitors against resistant virus

Abstract

Background: The AIDS epidemic has spread around the world at an alarming rate. Although the first generation of HIV protease inhibitors, including indinavir, nelfinavir, saquinavir, ritonavir and amprenavir, were initially effective against HIV infection, the fast emerging resistance to these agents has been a substantial and persistent problem in the treatment of AIDS. Attempts to address the resistance issue with ‘salvage therapy’ consisting of high doses of multiple protease inhibitors have only been moderately successful owing to the high level of cross-resistance and toxicities associated with the protease inhibitors. Objective: To study the second generation HIV protease inhibitors against resistant virus. Method: This review highlights new developments achieved by various organizations to address the challenge of high level resistance of current therapies since 2000. Conclusion: All second generation protease inhibitors used in patients who experienced extensive treatment require ritonavir as a pharmacological boosting agent to increase the drug level in the plasma, but there is toxicity associated with such a practice. Accordingly, there remains a need for new protease inhibitors with improved effectiveness against the resistant viral variants. A third generation protease inhibitor will require no boosting agent while maintaining high potency against resistant virus.

Keywords::

• HIV
• mutations
• resistant virus
• second generation protease inhibitors